NDLI: A study of the interaction between HIV-1 protease and C 2-symmetric inhibitors by computational methods

Content Provider	Springer Nature Link
Author	Shi, Shuhua Hu, Guodong Zhang, Xiumei Wang, Jihua
Copyright Year	2014
Abstract	The human immunodeficiency virus type 1 protease (HIV-1 PR) is a major target for the design of anti-AIDS (acquired immune deficiency syndrome) drugs. Some C 2-symmetric inhibitors have been designed for the C 2-symmetric binding pocket of HIV-1PR. The crystallographic structures reveal that the binding modes are not C 2-symmetric for C 2- symmetric inhibitors binding to PR. In this work, four molecular dynamics (MD) simulations were performed to investigate the binding modes between four C 2-symmetric inhibitors (6 AD, 6AG, 6FD and 6FG) and PR, as well as the stabilities of these inhibitors in the binding pocket. Analysis of the hydrophobic surface of the binding pocket shows that it is necessary to add a polar group to the P1 (benzyl) and P2 (phenyl) groups of the inhibitor 6AD. Analysis of the hydrogen bonds formed between inhibitors and residues (Asp25/Asp25′, Ile50/Ile50′) indicates that the steric structures of the inhibitors are not suitable for the binding pocket. The two increased polar groups of trifluoromethyl and formamido meet the needs of the binding pocket for polar molecules. The inhibitor with both these groups (6FG) has stronger stability than the other three inhibitors, which have only one (6AG and 6FD) or none (6AD) of these groups. The ranking of binding free energies calculated by molecular mechanics-generalized born surface area (MM-GBSA) method agrees well with the experimental data. It is expected that this study will provide theoretical guidance for the design of anti-AIDS drugs targeting HIV-1PR. Figure Left Inhibitor 6AD in the binding pocket of human immunodeficiency virus type 1 protease. Right Differences of free energies for trifluoromethyl and formaminde
Starting Page	1
Ending Page	10
Page Count	10
File Format	PDF
ISSN	16102940
Journal	Journal of Molecular Modeling
Volume Number	20
Issue Number	8
e-ISSN	09485023
Language	English
Publisher	Springer Berlin Heidelberg
Publisher Date	2014-07-15
Publisher Place	Berlin, Heidelberg
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	HIV-1 protease C 2-symmetric inhibitors Molecular dynamics simulation MM-GBSA Computer Applications in Chemistry Molecular Medicine Computer Application in Life Sciences Characterization and Evaluation of Materials Theoretical and Computational Chemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Physical and Theoretical Chemistry Computational Theory and Mathematics Catalysis Inorganic Chemistry Computer Science Applications

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